Sulfamates of the formula I: ##STR1## wherein X is O or CH.sub.2 and R.sub.1, R.sub.2, R.sub.3, R.sub.4, and R.sub.5 are as herein defined, are known compounds that have been found to exhibit anticonvulsant activity and thus are useful in the treatment of conditions such as epilepsy. These compounds are disclosed in U.S. Pat. Nos. 4,582,916 and 4,513,006, which also disclose processes for production of such compounds. The entire disclosure of these two patents are hereby incorporated herein by reference.
One reaction scheme disclosed in these prior art patents covers the reaction of an alcohol of the formula RCH.sub.2 OH with a chlorosulfamate of the formula ClSO.sub.2 NH.sub.2 or ClSO.sub.2 NHR.sub.1 in the presence of a base such as potassium t-butoxide or sodium hydride (NaH) at a temperature of about -20.degree. C. to 25.degree. C. and in a solvent such as toluene, tetrahydrofuran (THF) or dimethylformamide (DMF), wherein R is a moiety of the formula II: ##STR2##
This process has two major disadvantages. One disadvantage is that it calls for a combination of NaH and DMF which has an uncontrollable exotherm and is therefore potentially explosive. See J. Buckley et al., Chemical & Engineering News, Jul. 12, 1982, page 5; and G. DeWail, Chemical & Engineering News, Sep. 13, 1982. Another disadvantage is that the process also uses highly toxic and corrosive chlorosulfonyl isocyanate (CSI) to prepare the commercially unavailable sulfamyl chloride (ClSO.sub.2 NH.sub.2). The CSI is not only difficult to work with, because of its toxicity and corrosiveness, but also is available front only one commercial supplier.
Another known process disclosed in the above mentioned U.S. Pat. No. 4,513,006 for producing the compounds of formula I comprises the reaction of an alcohol of the formula RCH.sub.2 OH with sulfuryl chloride of the formula SO.sub.2 Cl.sub.2 in the presence of a base such as triethylamine or pyridine at a temperature of about -40.degree. C. to 25.degree. C. in a diethyl ether or methylene chloride solvent to produce a chlorosulfate of the formula RCH.sub.2 OSO.sub.2 Cl. The chlorosulfate of the formula RCH.sub.2 OSO.sub.2 Cl may then be reacted with an amine of the formula R.sub.1 NH.sub.2 at a temperature of about -40.degree. C. to 25.degree. C. in a methylene chloride or acetonitrile solvent to produce the compound of the formula I. This process (utilizing diethyl ether, methylene chloride and acetonitrile solvents) produces relatively low yields of the desired end product of formula I in comparison with the process of the present invention.
The final process disclosed in the two patents comprises the reaction of the chlorosulfate of formula RCH.sub.2 OSO.sub.2 Cl formed as described previously with a metal azide such as sodium azide in a solvent such as methylene chloride or acetonitrile to yield an azidosulfate of the formula RCH.sub.2 OSO.sub.2 N.sub.3. The azidosulfate is then reduced to a compound of the formula I wherein R.sub.1 is hydrogen, by catalytic hydrogenation. The disadvantage with this process is that explosions may occur when handling the azide compounds. Also the process contains an additional chemical transformation involving the reduction of the azide to the NH.sub.2 moiety.
It is an object of the present invention to provide a new and improved process for producing compounds of the formula I, which uses readily available materials, can be carried out under safe conditions and at relatively high yields. The advantages of the present invention are described in part below and in part will be obvious from this description and by comparison to the prior art processes described in the Examples section below.